Neurol Sci DOI 10.1007/s10072-014-1957-4
LETTER TO THE EDITOR
Should minor strokes be excluded from intravenous thrombolysis? Leonard L. L. Yeo • Rahul Rathakrishnan Prakash R. Paliwal • Vijay K. Sharma
•
Received: 4 September 2014 / Accepted: 15 September 2014 Ó Springer-Verlag Italia 2014
Dear Sir, We read with interest the review by Huang et al. [1] regarding intravenous thrombolysis for minor stroke and rapidly improving symptoms (MRIS). Although this review attempts to address an important clinical dilemma faced by stroke physicians on a daily basis, we strongly feel that one should be cautious in accepting the conclusion regarding futility of intravenous thrombolysis in MRIS. Intravenously administered tissue plasminogen activator (IV-tPA) remains the only approved drug therapy for achieving arterial recanalization in acute ischemic stroke (AIS) and improves the chances of favorable outcome. However, numerous contraindications need to be carefully excluded before initiating thrombolysis. Minor stroke is one such important contraindication for withholding IV thrombolysis due to uncertain benefits. Although, it was not an explicit contraindication, the pivotal NINDs thrombolysis trial included only 58 patients with minor stroke. Interestingly, 2,971 patients with minor or rapidly improving strokes were excluded from thrombolysis [2]. Similarly, about one-third of the 93,517 patients arriving to the hospital within 2 h were not treated with IV-tPA solely
L. L. L. Yeo (&) R. Rathakrishnan P. R. Paliwal V. K. Sharma Division of Neurology, Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, 119074 Singapore, Singapore e-mail: [email protected] V. K. Sharma Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
because of the milder or rapidly improving stroke. In a recent meta-analysis, we have shown that patients with mild strokes derive benefit from intravenous thrombolysis (pooled odds ratio 1.319; 95 % confidence interval, 1.004–1.733; z = 1.987; p = 0.047) without any significant increase in mortality [3]. It is important to look into the possible reasons for contradictory reports regarding the benefits of IV-tPA in MRIS. Huang et al. [1] considered minor stroke and rapidly improving symptoms as representing one entity, largely owing to the similar etiopathogenic mechanism. Perhaps, this approach influenced the overall results. Rapidly improving stroke and mild stroke may not always represent the same clinical entity. Accordingly, rapidly improving symptoms are expected in patients with large artery occlusion that recanalises spontaneously while the neurological deficits in a lacunar stoke are often mild and may persist. An important reason for contradictory results among various studies on patients with MRIS is the heterogeneity of data that introduce bias due to the approach taken when choosing studies to include. For example, Huang included the case series by Strbian et al. [4] which did not have control group outcome and the study by Mittal et al. [5] which did not report functional outcomes at 3 months. We feel that the current IV thrombolysis guidelines for mild or minor acute stroke are in need of revision to support the clinician who may feel that IV-tPA may benefit his patient, but are limited as the situation falls outside the published guidelines. Nonetheless, we congratulate Huang et al. on shedding light on this practically relevant aspect of acute stroke care. We look forward to the results of thrombolysis for minor ischemic stroke with proven acute symptomatic occlusion using Tenecteplase-tPA (TEMPO-1) trial, which is expected to put to rest the ambiguity faced by the front-line stroke neurologists.
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Neurol Sci
References 1. Huang Q, Ma Q, Jia J, Wu J (2014) Intravenous thrombolysis for minor stroke and rapidly improving symptoms: a quantitative overview. Neurol Sci 35:1321–1328 2. (1995) Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 333:1581–1587 3. Yeo LL, Ho R, Paliwal P, Rathakrishnan R, Sharma VK (2014) Intravenously administered tissue plasminogen activator useful in
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milder strokes? A meta-analysis. J Stroke Cerebrovasc Dis. 2014 Aug 9 [Epub ahead of print] PubMed PMID: 25113080 4. Strbian D, Piironen K, Meretoja A, Sairanen T, Putaala J, Tiainen M, Artto V, Rantanen K, Ha¨ppo¨la¨ O, Kaste M, Lindsberg PJ (2013) Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms. Int J Stroke 8:293–299 5. Mittal M, Rymer M, Lai SM (2012) Should all patients with mild ischemic stroke be excluded from therapeutic stroke trials? J Clin Neurosci 19:1486–1489
LETTER TO THE EDITOR
Should minor strokes be excluded from intravenous thrombolysis? Leonard L. L. Yeo • Rahul Rathakrishnan Prakash R. Paliwal • Vijay K. Sharma
•
Received: 4 September 2014 / Accepted: 15 September 2014 Ó Springer-Verlag Italia 2014
Dear Sir, We read with interest the review by Huang et al. [1] regarding intravenous thrombolysis for minor stroke and rapidly improving symptoms (MRIS). Although this review attempts to address an important clinical dilemma faced by stroke physicians on a daily basis, we strongly feel that one should be cautious in accepting the conclusion regarding futility of intravenous thrombolysis in MRIS. Intravenously administered tissue plasminogen activator (IV-tPA) remains the only approved drug therapy for achieving arterial recanalization in acute ischemic stroke (AIS) and improves the chances of favorable outcome. However, numerous contraindications need to be carefully excluded before initiating thrombolysis. Minor stroke is one such important contraindication for withholding IV thrombolysis due to uncertain benefits. Although, it was not an explicit contraindication, the pivotal NINDs thrombolysis trial included only 58 patients with minor stroke. Interestingly, 2,971 patients with minor or rapidly improving strokes were excluded from thrombolysis [2]. Similarly, about one-third of the 93,517 patients arriving to the hospital within 2 h were not treated with IV-tPA solely
L. L. L. Yeo (&) R. Rathakrishnan P. R. Paliwal V. K. Sharma Division of Neurology, Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, 119074 Singapore, Singapore e-mail: [email protected] V. K. Sharma Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
because of the milder or rapidly improving stroke. In a recent meta-analysis, we have shown that patients with mild strokes derive benefit from intravenous thrombolysis (pooled odds ratio 1.319; 95 % confidence interval, 1.004–1.733; z = 1.987; p = 0.047) without any significant increase in mortality [3]. It is important to look into the possible reasons for contradictory reports regarding the benefits of IV-tPA in MRIS. Huang et al. [1] considered minor stroke and rapidly improving symptoms as representing one entity, largely owing to the similar etiopathogenic mechanism. Perhaps, this approach influenced the overall results. Rapidly improving stroke and mild stroke may not always represent the same clinical entity. Accordingly, rapidly improving symptoms are expected in patients with large artery occlusion that recanalises spontaneously while the neurological deficits in a lacunar stoke are often mild and may persist. An important reason for contradictory results among various studies on patients with MRIS is the heterogeneity of data that introduce bias due to the approach taken when choosing studies to include. For example, Huang included the case series by Strbian et al. [4] which did not have control group outcome and the study by Mittal et al. [5] which did not report functional outcomes at 3 months. We feel that the current IV thrombolysis guidelines for mild or minor acute stroke are in need of revision to support the clinician who may feel that IV-tPA may benefit his patient, but are limited as the situation falls outside the published guidelines. Nonetheless, we congratulate Huang et al. on shedding light on this practically relevant aspect of acute stroke care. We look forward to the results of thrombolysis for minor ischemic stroke with proven acute symptomatic occlusion using Tenecteplase-tPA (TEMPO-1) trial, which is expected to put to rest the ambiguity faced by the front-line stroke neurologists.
123
Neurol Sci
References 1. Huang Q, Ma Q, Jia J, Wu J (2014) Intravenous thrombolysis for minor stroke and rapidly improving symptoms: a quantitative overview. Neurol Sci 35:1321–1328 2. (1995) Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 333:1581–1587 3. Yeo LL, Ho R, Paliwal P, Rathakrishnan R, Sharma VK (2014) Intravenously administered tissue plasminogen activator useful in
123
milder strokes? A meta-analysis. J Stroke Cerebrovasc Dis. 2014 Aug 9 [Epub ahead of print] PubMed PMID: 25113080 4. Strbian D, Piironen K, Meretoja A, Sairanen T, Putaala J, Tiainen M, Artto V, Rantanen K, Ha¨ppo¨la¨ O, Kaste M, Lindsberg PJ (2013) Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms. Int J Stroke 8:293–299 5. Mittal M, Rymer M, Lai SM (2012) Should all patients with mild ischemic stroke be excluded from therapeutic stroke trials? J Clin Neurosci 19:1486–1489
